CDH13、PCDH8基因启动子甲基化与卵巢癌患者临床病理特征和预后的关系  

Relationships between CDH13,PCDH8 gene promoter methylation and clinicopathological features and prognosis of ovarian cancer patients

作　　者：王玎[1,2] 李志英[1,2] 李会 卢娇[1,2] WANG Ding;LI Zhiying;LI Hui;LU Jiao(Department of Gynaecology,Affiliated Renhe Hospital of China Three Gorges University,Yichang 443001,China;不详)

机构地区：[1]三峡大学附属仁和医院妇科,湖北宜昌443001 [2]三峡大学妇科肿瘤研究所

出　　处：《山东医药》2022年第13期12-17,共6页Shandong Medical Journal

基　　金：湖北省教育厅科学研究计划项目(D20151202);宜昌市医疗卫生科研项目(A21-2-043)。

摘　　要：目的探讨钙黏蛋白13(CDH13)、原钙黏蛋白8(PCDH8)基因启动子甲基化与卵巢癌患者临床病理特征和预后的关系。方法选择接受根治性或姑息性手术的卵巢癌患者203例,取手术切除的卵巢癌组织与癌旁正常组织,采用Western blotting法检测CDH13、PCDH8蛋白表达,采用甲基化特异性PCR法检测CDH13、PCDH8基因启动子甲基化状态。收集卵巢癌患者临床病理资料,分析CDH13、PCDH8基因启动子甲基化状态与患者临床病理特征和预后的关系,采用多因素Cox比例风险回归模型分析卵巢癌患者预后不良的危险因素。结果卵巢癌组织CDH13、PCDH8蛋白相对表达量均低于癌旁正常组织(t分别为-15.754、-11.666,P均<0.01)。卵巢癌组织CDH13、PCDH8基因启动子甲基化阳性率均高于癌旁正常组织(χ^(2)分别为127.459、192.718,P均<0.01)。卵巢癌组织CDH13、PCDH8基因启动子甲基化阳性与TNM分期、淋巴结转移有关(P均<0.05),而与年龄、肿瘤直径、组织分化程度无关(P均>0.05)。截至2021年6月,共随访5~60个月、中位随访时间42个月,随访期间死亡77例。卵巢癌组织CDH13、PCDH8基因启动子甲基化阳性患者5年累积生存率均低于卵巢癌组织CDH13、PCDH8基因启动子甲基化阴性患者(χ^(2)分别为11.087、14.796,P均<0.05)。多因素Cox比例风险回归分析发现,TNM分期Ⅲ、Ⅳ期及有淋巴结转移、CDH13基因启动子甲基化阳性、PCDH8基因启动子甲基化阳性均为卵巢癌患者预后不良的独立危险因素(P均<0.05)。结论卵巢癌组织CDH13、PCDH8基因启动子甲基化阳性明显升高,并且与肿瘤TNM分期、淋巴结转移以及患者预后密切相关。Objective To investigate the relationships between cadherin 13(CDH13)and protocadherin 8(PCDH8)gene promoter methylation and the clinicopathological characteristics and prognosis of ovarian cancer patients.Methods Totally 203 patients with ovarian cancer who underwent radical or palliative surgery were selected,and the surgically resected ovarian cancer tissues and adjacent normal tissues were taken.Western blotting was used to detect CDH13 and PCDH8 protein expression,and methylation-specific PCR was used to detect CDH13 and PCDH8 gene promoter methylation status.The clinicopathological data of ovarian cancer patients were collected,and we analyzed the relationships between CDH13 and PCDH8 gene promoter methylation status and clinicopathological characteristics and prognosis,and the multi-factor Cox proportional hazards regression model was used to analyze the risk factors for poor prognosis of ovarian cancer patients.Results The relative expression levels of CDH13 and PCDH8 protein were lower in the ovarian cancer tissues than in the normal tissues adjacent to the cancer(t=-15.754,-11.666,both P<0.01).The positive rates of CDH13 and PCDH8 gene promoter methylation were higher in the ovarian cancer tissues than in the normal tissues adjacent to the cancer(χ^(2)=127.459,192.718,both P<0.01).Positive promoter methylation of CDH13 and PCDH8 genes in the ovarian cancer tissues were related to TNM stage and lymph node metastasis(all P<0.01),but not to age,tumor diameter,or degree of tissue differentiation(all P>0.05).As of June 2021,the total follow-up time ranged from 5 to 60 months,with a median follow-up time of 42 months,and 77 died during the follow-up period.The 5-year cumulative survival rates of patients with positive promoter methylation of CDH13 and PCDH8 genes in ovarian cancer tissues were lower than those of patients with negative promoter methylation of CDH13 and PCDH8 genes in ovarian cancer tissues(χ^(2)=11.087,14.796,all P<0.05).Multi-factor Cox proportional hazards regression analysis revealed tha

关 键 词：卵巢癌 钙黏蛋白13 原钙黏蛋白8 基因启动子甲基化 临床病理特征 预后 

分 类 号：R737.31[医药卫生—肿瘤]